Many surgical procedures carry the risk of accidental nerve damage or transection, which can result in significant problems such as chronic pain or paralysis. There has been research in the use of near-infrared (NIR) agents to highlight nerve tissue during surgery, thereby enhancing the surgeon's ability to avoid cutting or damaging the highlighted nerve tissue. For example, molecules such as distyrylbenzene and oxazine derivatives have been used, but they lack the necessary binding characteristics and/or spectral properties needed to be effective for intraoperative use in humans and other mammals.
Whitney et al. identified several nerve binding polypeptides by applying phage display methodologies against excised murine peripheral nerves (Whitney, M. A.; Crisp, J. L.; Nguyen, L. T.; Friedman, B.; Gross, L. A.; Steinbach, P.; Tsien, R. Y.; Nguyen, Q. T. Nat. Biotech. 2011, 29, 352). The sequences were subsequently labeled with a fluorophore or NIR dye, and evaluated in vitro and in vivo for binding. The sequence that provided the highest contrast over background was a 17-residue polypeptide, NP41 (FIG. 1A). There is a need for nerve-binding agents with enhanced selectivity for nerve tissue and for improved spectral properties for intraoperative use.